P1641: ELTROMBOPAG TREATMENT, OUTCOMES AFTER DISCONTINUATION IN ADULT PATIENTS WITH PRIMARY IMMUNE THROMBOCYTOPENIA, AND EXPLORATION OF POTENTIAL PREDICTIVE FACTORS: A REAL-WORLD CLINICAL EXPERIENCE
Authors: X. Liu, R. Fu, H. Li, Y. Chen, W. Liu, F. Xue, L. Zhang, R. Yang
Journal: HemaSphere (2022)

Background: Immune thrombocytopenia (ITP) is an acquired autoimmune disorder characterized by accelerated platelet destruction and impaired platelet production. Eltrombopag has been widely used in ITP in clinical practice for over a decade, however, there is limited evidence on predictors of response and successful discontinuation. Aims: To ascertain the optimal initial dose for East Asian descent, and explore the clinical and biological markers for adequate response. Besides, to investigate the potential for successful discontinuation in ITP patients treated with eltrombopag in a real-world setting and its clinical predictors. Methods: We retrospectively evaluated 244 adult primary ITP patients. All patients were hospitalized at our institution between January 2016 and October 2020 and treated with eltrombopag. Patient and disease characteristics, clinical outcomes, and adverse events (AEs) during eltrombopag treatment, were investigated. Blood samples were also obtained at baseline to detect the number of lymphocytes and the expression of subsets and other autoantibodies. Patients achieved overall response were divided into three groups (R1: 30-49, R2: 50-99, R3: ≥100 × 10⁹/L) according to platelet counts, which was used to analyze the potential predictors of response and successful discontinuation. Sustained response off-treatment (SRoT) was defined as platelet count ≥30 × 10⁹/L for at least 1 month with no ITP medication. Results: The initial daily dose was 25 mg for 20 patients (8.2%), 50 mg for 129 patients (52.9%), 75 mg for 95 patients (38.9%), respectively. The overall response rate was 187/244 (76.6%), with 26/244 achieving R1 (10.7%), 49/244 achieving R2 (20.1%), and 112/244 achieving R3 (45.9%). The median of time to response (TTR) was 5 days (IQR: 3-11). Multivariable logistic analysis revealed that significant predictors of adequate response included female gender (OR=3.10, p=0.0377), less prior ITP therapies (OR=1.552, p=0.0103), less combination medication (OR=1.53, p=0.0328), lower maximum dose (OR= 6.637, p=0.0041), and more naive Treg/T cell % (OR=3.79, p=0.0120). Higher baseline megakaryocyte count was found to be significant correlated with less TTR (r=-0.191, p=0.022), while there was no significant correlation between the megakaryocytes count and the response rate (r=-0.009, p=0.894). A total of 60 treatment-related AEs was reported, which were mainly of CTCAE grade 1 or 2 in intensity. No thromboembolic events were observed during hospitalization; no thrombotic events, stroke or myocardial infarction requiring medical intervention were reported during follow-up period. Eltrombopag was discontinued in 81 responders. Patients who failed to maintain platelet counts, who switched to other medications or underwent splenectomy were all considered relapse. A total of 29 patients (35.8%) observed SRoT after discontinuing eltrombopag. The multivariable analysis identified that response degree was a predictive factor of SRoT (p = 0.0007, Table 1), in which the SRoT rate was up to 53.2% in patients achieved R3. Image:Summary/Conclusion: In clinical practice, most East Asian patients with higher initial dose obtained better short-term response and had an acceptable safety profile. Patients treated with eltrombopag in earlier lines, with less combination medication, with lower maximum dose, and higher Naive Treg/T cell (%) may achieve an adequate response. The higher number of megakaryocytes could potentially be associated with faster response. The higher SRoT rate in R3 patients encourages to taper eltrombopag in such patients.